Human granulocyte lysosomal elastase is a protease capable of inducing emphysema-like lesions in the lungs of animals similar to those seen in the advanced stages of the human disease. Alpha 1 antitrypsin (AlAT) is the major serum inhibitor of elastase. The proteolysis theory of emphysema states that protease-antiprotease imbalances are responsible for lung destruction. The presence of pulmonary function abnormalities in patients with COPD cannot be explained solely by quantitative differences in A1AT or in granulocyte elastase. We have observed an increased number of COPD patients, when compared with controls who continue to demonstrate elastase activity after mixing their lysosomal extracts containing elastase with their plasma fractions containing A1AT. A hypothesis arising from this observation states that the ability of serum protease inhibitors to control elastolytic activity may be impaired. This hypothesis will be tested by measuring proteolytic activity against insoluble elastin and the amount of amidase activity against a flourogenic elastase substrate after combining autologous plasma and granulocyte lysosomal extracts of COPD patients and of normal subjects. Those proteins in plasma or lysosomal extracts contributing to this "unrestricted" elastolytic activity will be purified by column chromotography. Attempts will be made to identify these molecules using antisera to known human proteins. The amounts of unrestricted proteolysis will be compared to the degree of pulmonary abnormality utilizing tests for FEV1, MMF, VC, DLCO.